Nanostructure, applied device and preparation method thereof

Description

FIELD OF THE INVENTION

[0001] The present invention relates to a nanostructure and the preparation method for the nanostructure, as defined in the claims. The nanostructure of the present invention has the abilities of absorbing a near infrared ray, exhibiting a non-linear optical property and generating a two-photon fluorescence.

BACKGROUND OF THE INVENTION

[0002] In recent years, nano-materials and nanotechnology have become the key point for research in every nation. A nanomaterial usually refers to a material with a size range from 1 nm to 100 nm. Since nanoparticles have a very small particle size and the number of atoms constituting the nanoparticle is far less than the typical particle, it thus has a great surface area and a high surface atomic ratio, and thereby the nanoparticle itself has a quantum effect. Therefore, nanoparticles have many specific properties and potential applications in the aspects of the catalyst, the electrode, the optical property and the mechanical property. Hence, nanomaterials and nanotechnology can be applied to various fields that have developmental potential.

[0003] Among the many metal materials for producing nanoparticles, gold was the earliest one to be investigated generally. Gold nanoparticles are considered as the best material for use in the living body due to its many advantages such as simple preparation method and high biocompatibility, such that biomedical research and development of gold nanoparticles has increased year by year.

[0004] The near infrared ray (NIR), especially between the region 1000∼1350 nm, is known as the biological window in which the electromagnetic wave has better tissue penetration while not being absorbed by the skin tissue to achieve the detection and treatment for the deep tissues. Meanwhile, the biological tissue significantly reduces generation of autofluorescence when irradiated by the NIR. It goes without saying that a material that has the abilities of absorbing the NIR and generating the fluorescence can be applied in the biomedical field. However, an NIR-absorber with a size less than 100 nm is not available in that region, and so the application of the NIR-absorber in the living body is limited. Bardhan et al. disclose in J. Phys. Chem., 114, 2010, 7378-7383, Au core nanospheres, surrounded by a silica layer and an outer gold shell, which has an overall size of less than 100 nm and enhanced absorption in the NIR "water-window". Zhu Jian et al. disclose in Plasmonics, 6(3), 2011, 527-534, dielectric coated gold nanospheres surrounded by a gold-shell layer.

[0005] In view of the drawbacks of the prior art, the present invention describes a nanostructure which has a dominant component of gold having the ability of absorbing the NIR, and has the functions of combining the targeted drug, imaging and treatment. This nanostructure can serve as an imaging agent to combine with existing ultrasound and endoscope technology currently in development to become a novel diagnostic and treatment platform and to provide more applications. The summary of the present invention is below.

SUMMARY OF THE INVENTION

[0006] In the nanostructure described in the present invention, a nanoparticle, which is an Au nanorod, shell, which is an Au/Ag alloy, encapsulating the nanoparticle and a gap are included, wherein the gap has a width ranging from 1.0 nm to 6.0 nm and is located between the nanoparticle and the shell to enable the nanostructure to generate a fluorescence, wherein the nanostructure absorbs a near infrared ray of 1000 nm to 1350 nm in wavelength.

[0007] In another aspect, the present disclosure describes a near infrared ray absorption device including an input end and an output end, wherein the input end absorbs a near infrared ray having a wavelength between 1,000 nm and 1,350 nm and the output end releases the fluorescence.

[0008] In addition, the present invention also describes a method for preparing said nanostructure, including (a) providing a nanoparticle, which is an Au nanorod, having a surface, (b) forming a metal layer, which is an Ag layer, on the surface of the nanoparticle, and (c) mixing the nanoparticle and the metal layer with an Au ion solution of 1mM to form a core-shell structure for the nanostructure, wherein the Au ion solution has a volume being 0.8 to 2 fold that of the nanoparticle, as defined in the claims.

[0009] The nanostructure of the present invention represents a breakthrough in the limitations of the NIR wavelength and the particle size of the past, which has sufficient originality for revolutionary change in the existing non-optical imaging and therapeutic technology (i.e. endoscope and ultrasound) field. Because the nanostructure of the present invention has the abilities of absorbing the NIR and emitting the fluorescence, it can be applied to the biomedical field as well as the optical field. The present nanostructure can serve as an imaging agent and can be combined with ultrasound or endoscope devices to develop novel diagnostic and treatment platforms. In addition to solving the existing problems, the present nanostructure also provides additional applications to eliminate the limitations in the use of the infrared ray.

[0010] Other objects, advantages and efficacies of the present invention are described in detail below and taken from the preferred embodiments with reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] 

Fig. 1 is an absorbance spectra analysis of the nanostructures with different gaps prepared according to the preparation method of the present invention.

Fig. 2 is a diagram showing the process by which the nanostructure of the present invention combines with the photosensitizer to serve as a non-linear optical imaging contrast or a photodynamic therapeutic agent.

Fig. 3 is a diagram showing the results of combining the nanostructure of the present invention with the photothermal therapy to treat tumors in mice.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] Examples - The following examples are provided to describe particular embodiments.

[0013] The present invention provides a nanostructure having a basic core-shell structure, wherein the core is an Au nanorod, and there is a gap having a width ranging from 1.0 nm to 6.0 nm between the Au nanorod and the shell, which is an Au/Ag alloy, such that the nanostructure has the ability of generating the fluorescence. The luminescence ability of the nanostructure is due to its ability to absorb NIR (in particular, the 1000∼1350 nm NIR), such that the NIR hyperthermia generates the non-linear optical property and the two-photon fluorescence by absorbing the thermal energy of the NIR.

[0014] The difference between the present nanostructure and the common nanoparticle resides in the gap between the core and the shell, the size of which can be regulated by the preparation method provided in the present invention. In the nanostructure prepared by the preparation method of the present invention, the gap having a width ranging between 1.0 nm and 6.0 nm demonstrates good absorbability to the NIR in the 1000 to 1350 nm wavelength, and this ability can not be achieved by the common nanostructure.

[0015] It can be observed through the use of a transmission electron microscope (TEM) that the nanostructure of the present invention has a core-shell structure. The TEM image shows that the nanostructure of the present invention has a length of about 53.2 nm, a width of about 22.1 nm, a gap between the core and shell of about 2.0 nm and a shell having a thickness of about 6.2 nm.

[0016] According to one aspect of the present disclosure, the core of the nanostructure is a gold (Au) nanoparticle. Since Au has high biocompatibility, the Au nanoparticle is considered as a material most applicable for use in a living body. Accordingly, the nanostructure of the present invention having a dominant material of Au can be generally applied to various medical platforms such as ultrasound, endoscopy and computer tomography, or be combined with other agents (e.g., photosensitizer) to serve as a non-linear optical imaging contrast tool and a photodynamic therapeutic agent, and thus integrate diagnostic and therapeutic applications.

[0017] The material of the shell of the present disclosure can be selected from one of gold (Au), silver (Ag), platinum (Pt), palladium (Pd), nickel (Ni) and an alloy thereof. In one aspect of the present disclosure, the material of the core is Au while that of the shell is Ag. According to the present invention, the material of the core is Au in the form of an Au nanorod while that of the shell is an Au-Ag alloy.

[0018] Since the present nanostructure has the abilities of absorbing the NIR, exhibiting a non-linear optical property and generating a two-photon fluorescence, it can be utilized as an energy transfer device (in particular the NIR absorbing device) where its input end can absorb the NIR having a wavelength between 1000 nm and 1350 nm and its output end releases the fluorescence. Actually, the NIR absorbing device is a nanostructure with a size smaller than 100 nm, and thus it can be applied to a living body such as a mammal so that the process of the energy transfer as described above occurs in the body and facilitates the image analysis and drug delivery.

[0019] In order to prepare the above nanostructure, the present invention provides a preparation method including (a) providing an Au nanorod having a surface, (b) forming an Ag layer on the surface of the nanoparticle, and (c) mixing the nanoparticle and the Ag layer with an Au ion solution 1 mM to form a core-shell structure for the nanostructure, wherein the Au ion solution has a volume being 0.8 to 2 fold that of the nanoparticle, as defined in the claims.

[0020] According to the present disclosure, the nanoparticle may include a nanotube, a nanorod and a nanowire. According to the present invention, the nanoparticle is an Au nanorod. The material of the metal layer may, according to the disclosure, be one selected from Au, Ag, Pt, Pd, Ni and an alloy thereof. In the above step (c), the Au ion solution is added in order to regulate the gap between the core and the shell. The Au ion solution used in the embodiment of the present invention is chloroauric acid (HAuCl₄) which has a volume being 0.8 to 2 fold that of the nanoparticle, preferably 0.8 to 1.5 fold.

[0021] The embodiments for preparing the nanostructure of the present invention are described in detail below.

Preparation of Au nanorods

[0022] In each of two 50 ml centrifuge tubes, 1.822 g of cetyltrimethylammonium boride (CTAB) and 5.4 ml of 5 mM chloroauric acid (HAuCl₄·3H₂O) are uniformly mixed with water to prepare a solution having a volume of 50 ml. When the CTAB is completely dissolved, the solution becomes an orange, clear solution.

[0023] The two tubes of 50 mL CTAB mixed solution are poured into a flask and stirred, and then 60 µL of 0.1M silver nitrate (AgNO₃) is added to the flask. After uniformly mixing the solution, 600 µL of 0.1M ascorbic acid is added to the flask within 5 minutes, which creates a colorless transparent solution. Following the addition of the ascorbic acid, 40 µL of 10 mM sodium borohydride (NaBH₄) is added within 5 seconds to react for 2 hours, which creates a reddish brown solution. The resulting product is collected in a centrifuge at 10,000 rpm for 20 minutes to remove the supernatant, the precipitate is washed with ultrapure water and centrifuged again at 10,000 rpm for 20 minutes to remove the supernatant and to collect the precipitate in the tube. Finally, the precipitate is redispersed in ultrapure water, and the macro molecules are centralized at the lower layer of the tube at 2,000 rpm for 30 minutes. The upper layer is removed and put into a new tube.

Synthesis of Au/Ag Core-shell Nanorods

[0024] 500 µL of 100 ppm Au nanorod solution and 500 µL of 100 mM CTAB are mixed to form 1 mL of a mixture containing 50 mM CTAB and 50 ppm Au nanorods. 5 mL of 1 wt% poly(vinylpyrrolidone) (PVP) is poured into a vial, and 1 mL of the mixture containing 50 mM CTAB and 50 ppm Au nanorods is added to the vial.

[0025] 950 µL of 1 mM AgNO₃ solution and 125 µL of 100 mM ascorbic acid solution are added into the vial and uniformly mixed through stirring. 0.25 mL of 100 mM sodium hydroxide solution is then added to the mixture to react with the mixture for 10 minutes. When the color of the solution changes, it means that the Ag nano layer has formed on the Au nanorod, and the final color of this solution is citrus red. The product is collected by using a centrifuge at 10,000 rpm for 10 minutes to remove the supernatant, and the precipitate is washed with deionized water. The precipitate is centrifuged at 10,000 rpm for 10 minutes again to remove the supernatant, and the precipitate is redispersed with deionized water to become a 1 mL solution. The end product is the Au/Ag core-shell nanorod which is covered with an Ag nanolayer.

[0026] As shown in Fig. 1, the size of the gap can be controlled through different experimental conditions (i.e. by changing the volume of the Au ion solution). The size of the gap will affect the intensity of the NIR absorbance. The methods for preparing nanoparticles with different sizes of the gap are as follows.

Syntheses of the nanostructure of Au nanorod in Au/Ag alloy shell with 2 nm and 6.5 nm gaps

[0027] The nanostructure of Au nanorod in Au/Ag alloy shell with 2 nm gap

[0028] 1 mL Au/Ag core-shell nanorod solution, 500 µL of 100 mM CTAB solution, 125 µL of 100 mM ascorbic acid and 700 µL of 1 mM Au ion solution are in turn added to 5375 µL of deionized water at room temperature and stirred for 15 minutes. The solution is the nanostructure of Au nanorod in Au/Ag alloy shell with a 2 nm gap and should be calp.

The nanostructure of Au nanorod in Au/Ag alloy shell with 6.5 nm gap

[0029] 1 mL Au/Ag core-shell nanorod solution, 500 µL of 100 mM CTAB solution, 125 µL of 100 mM ascorbic acid and 400 µL of 1 mM Au ion solution are in turn added to 5375 µL of deionized water at room temperature and stirred for 15 minutes. The solution is the nanostructure of Au nanorod in Au/Ag alloy shell with a 6.5 nm gap and should be hyacinthine.

[0030] The products of the above reactions are centrifuged at 10,000 rpm for 10 minutes. After the supernatant is removed, the products are washed with saturated brine and centrifuged again at 10,000 rpm for 10 minutes to remove the supernatant. The resulting precipitates are washed with deionized water and centrifuged at 10,000 rpm for 10 minutes. The final products are redispersed in deionized water to form a 1 mL solution.

[0031] Based on the above disclosures, it can be known that the core-shell nanostructure changes from the Au/Ag core-shell nanostructure to the Au nanorod in Au/Ag alloy shell nanostructure after the gap is generated. This means that the gap is generated inside the original Au nanorod to create the Au/Ag alloy shell.

[0032] As shown in Fig. 1, the Au nanorod in Au/Ag alloy shell nanostructure with different gap sizes can be controlled by changing the volume of the Au ion solution. According to the above preparation methods, the Au nanorod in Au/Ag alloy shell nanostructures with 2 nm, 4 nm and 6.5 nm gaps are prepared and their absorbance to NIR with different wavelengths are measured. The measurements show that the nanostructures with 2 nm and 4 nm gaps have better absorbance while the nanostructure with 6.5 nm gap has weaker absorbance to NIR higher than the 600 nm wavelength. In order to prepare a nanostructure having good absorbance to NIR at wavelengths ranging between 1,000 and 1,350 nm, the width of the gap is preferably set between 1.0 nm and 6.0 nm.

[0033] According to the embodiment of the present invention, the nanostructures with 2 nm and 6.5 nm gaps are obtained by adding 700 µL and 400 µL of the 1mM Au ion solution into the solution containing the Au/Ag core-shell nanorods. Because the starting material for preparing the Au nanorod-Au/Ag alloy shell nanostructure is 500 µL of Au nanorod solution containing 100 ppm Au, it is estimated therefrom that the volume of the Au ion solution is about 0.8 to 2 fold that of the nanoparticle, preferably 0.8 to 1.5 fold, so as to generate nanostructures with better NIR absorbance.

[0034] The various specific solutions used in the above preparations such as the CTAB, the HAuCl₄, and the AgNO₃ solutions, are only exemplary embodiments. For example, the CTAB used in the above embodiments is cetyltrimethylammonium boride, but the skilled person in the art should realize that the surfactants with different chain lengths (i.e. the surfactant with 4 to 18 carbon chains) may be used to prepare the nanostructures in the present invention.

The ex vivo test of the present nanostructures

[0035] The present nanostructures prepared by the above preparation methods are mixed with A549 cancer cells. The A549 cells are pre-treated with a solution containing 8.7x 10¹⁰ particle/mL Au nanorod-Au/Ag alloy shell nanostructure or a solution containing Au nanorod-Au/Ag alloy shell nanostructure modified with toluidine blue O (TBO). Then, the cells are irradiated with a 1230 nm laser (6.5 x 10⁶ W/cm²), and the cell viability is observed at different points in time. The result of mixing the Au nanorod-Au/Ag alloy shell nanostructure with the cells shows that the cells are not damaged and maintain the same morphology over time. However, the result of mixing the Au nanorod-Au/Ag alloy shell nanostructure modified with TBO with the cells shows that the cells begin to die and cell atrophy is generated over time.

[0036] After the Au nanorod-Au/Ag alloy shell nanostructure modified with TBO is injected into the vessel of the a mouse's ear, an in vivo test is performed by irradiating the ear with a 1230 nm laser, and the images of the mouse's ear are observed by a fluorescence microscope. Based on the two-photo fluorescence image, the third-harmonic generation image and the second-harmonic generation image observed by the fluorescence microscope, it can be seen that the Au nanorod-Au/Ag alloy shell nanostructure modified with TBO penetrates the vessel into the surrounding tissues and remains when it is injected into the mouse's ear. The fluorescence of the material can be detected when an external light source irradiates the mouse, which indicates that the material has the function of imaging detection in vivo.

[0037] Based on the above results, it is known that the present nanostructure not only facilitates the death of the cancer cells via the laser irradiation in the ex vivo study, but also inhibits the growth of the tumor via the laser irradiation in the in vivo study. Therefore, the present nanostructure has the potential to be developed as a therapeutic tool for cancer in mammals. The multi-functional nanomaterial provided in the present invention can be combined with ultrasound, a mature clinical procedure, and the developing non-linear optical endoscope, while it also has the potential to become a computer chromatography agent.

[0038] The nanostructure can be combined with a photosensitizer to serve as a non-linear optical image contrast tool and an agent for the photodynamic therapy.

The Au nanorod-Au/Ag alloy shell nanostructure where the surface is modified with a photosensitizer, TBO

[0039] 1mL of Au nanorod-Au/Ag alloy shell nanostructure is placed into a glass bottle and 67 µL of 7.5 mM 3-mercaptopropionic acid (MPA) is added thereto and incubated in a sonicator for 2 hrs. Subsequently, the mixture is incubated at room temperature overnight and then centrifuged at 10,000 rpm for 10 minutes. The supernatant is removed, and the precipitate is washed with deionized water and centrifuged at the same speed for 10 minutes again. The resulting supernatant is removed, and the precipitate is re-dispersed in a phosphate buffer solution (PBS) (pH 5.5) to form 1 mL solution and placed in a glass sample bottle. Then, 50 µL of 10 mM crosslinker (EDC/NHS) is added to the bottle and the bottle is incubated in the sonicator for 30 minutes. 130 µL of 30 µM TBO is added into the bottle to resume the sonication for 6 hrs, and the mixture is centrifuged at 10,000 rpm for 10 minutes to remove the supernatant. The precipitate is washed with deionized water and this step is repeated twice, and the final product is re-dispersed in the PBS buffer solution (pH5.5) to form 1 mL solution.

Modifying with the PEG molecular on the surface of the Au nanorod-Au/Ag alloy shell nanostructure modified with a photosensitizer TBO

[0040] The product resulting from the above steps is placed in a glass sample bottle, 50 µL of 10 mM crosslinker EDC/NHS is added to the bottle and the bottle is placed in a sonicator for 30 minutes. 100 µL of 10 µM PEG is added to the bottle, the sonication is resumed for 6 hrs, and the mixture is centrifuged at 10,000 rpm for 10 minutes to remove the supernatant. Then, the precipitate is washed with deionized water and this step is repeated twice, and the final product is re-dispersed in deionized water to form 1 mL solution.

[0041] Fig. 2 is a diagram showing the process by which the nanostructure of the present invention combines with the photosensitizer to serve as a non-lineal optical imaging contrast or a photodynamic therapeutic agent. As shown in Fig. 2, the nanostructure of the present invention has a core being an Au nanorod (Au NR) and a shell. The nanostructure is modified with a photosensitizer TBO on the surface thereof and then modified with the PEG according to the above-mentioned preparations, such that it may be used as an image contrast and a photodynamic therapeutic agent. Since the present nanostructure absorbs the NIR at 1,000-1,350 nm, it will emit the two-photon fluorescence (615 nm) under the irradiation of the NIR (e.g., at 1230 nm). This 615 nm fluorescence will be absorbed by the TBO to generate singlet oxygen that is toxic to the cancer cells. The process in which the fluorescence generated by the nanostructure is absorbed by the TBO thereon is referred as fluorescence resonance energy transfer (FRET). The nanostructure not only provides the function of image analysis but also causes the toxic effect to the cancer cells because it can release the fluorescence and the singlet oxygen (¹O₂).

An example of photothermal therapy

[0042] Fig. 3 is a diagram showing the results of the present invention with the photothermal to treat tumors in mice. The photothermal therapeutic test is performed where the Au nanorod-Au/Ag alloy shell nanostructure with the 2 nm gap (that absorb the NIR) and the 6.5 nm gap (that does not absorb the NIR) are compared with a control group. As shown in Fig. 3, these materials were injected into the tumors of the mice, and the mice were irradiated by a 1,024 nm laser for 7 minutes on days 0, 2, 4, 7 and 10. In the control group where the mice were not injected with the Au nanorod-Au/Ag alloy shell nanostructure, the tumor size increased over time, which indicates that the laser irradiation alone cannot provide the therapeutic effect. In the experimental group where the mice were injected with the Au nanorod-Au/Ag alloy shell nanostructure having the 6.5 nm gap, the tumor size also increased over time because the Au nanorod-Au/Ag alloy shell nanostructure having the 6.5 nm gap cannot absorb the NIR and thus does not cause any therapeutic effect, although the mice were injected with the material and irradiated. In the experimental group where the mice were injected with the Au nanorod-Au/Ag alloy shell nanostructure having the 2 nm gap, the tumor size decreased over time and even almost disappeared. This is because the Au nanorod-Au/Ag alloy shell nanostructure having the 2 nm gap absorbs the NIR and generates hyperthermia so as to kill the cancer cells, and therefore the therapeutic effect is increasingly effective over time.

[0043] In another medical application, the present nanostructure has the non-linear optical property so as to develop as a novel endoscope diagnostic and therapeutic technique when combined with an endoscope. The present nanostructure may deliver the drug via the endoscope and break through the limitation of using a near infrared light source in the past, in additional to providing images. In addition, the present nanostructure can also be combined with ultrasound therapeutic techniques to provide a structural analysis function that breaks through the limitation of traditional ultrasound, which detects only the shape or dissection. It can be seen that the applications of the present nanostructure are widespread and can be multiplied so as to generate a revolutionary change in existing non-optical imaging and therapeutic techniques.

Claims

1. A nanostructure, characterized by comprising:

an Au nanorod;

a shell encapsulating the Au nanorod and being an Au/Ag_alloy; and an empty gap having a width ranging from 1.0 nm to 6.0 nm, and located between the Au nanorod and the shell,

wherein the nanostructure absorbs a near infrared ray of 1,000 nm to 1,350 nm in wavelength.

2. A nanostructure as claimed in Claim 1, characterized in that the nanostructure further exhibits a non-linear optical property and generates a two-photon fluorescence.

3. A nanostructure as claimed in Claim 1 or 2, characterized in that the nanostructure has a size smaller than 100 nm, and the shell has a thickness between 2 nm and 7 nm.

4. A nanostructure as claimed in any one of Claims 1 to 3, characterized in that the nanostructure is combined with a photosensitizer to carry out an image analysis and a drug delivery for a mammal.

5. A method for preparing a nanostructure, characterized by comprising steps of:

(a) providing an Au nanorod having a surface;

(b) forming an Ag layer on the surface of the Au nanorod; and

(c) mixing the Au nanorod and the Ag_layer with an Au ion solution of 1 mM to form a core-shell structure for the nanostructure, wherein the Au ion solution has a volume being 0.8 to 2 fold that of the Au nanorod, and the core-shell structure absorbs a near infrared ray of 1,000 nm to 1,350 nm in wavelength, and includes a core, a shell and an empty gap formed between the core and the shell and having a width ranging from 1.0 nm to 6.0 nm.

6. A method as claimed in Claim 5, characterized in that step (c) further comprises an addition of an ascorbic acid solution.

7. A method as claimed in Claim 5 or 6, characterized in that the Au ion solution is a choloroauric acid which has a volume of 0.8 to 1.5 fold that of the Au nanorod.

8. A method as claimed in any one of Claims 5 to 7, characterized in that the shell has a thickness between 2 nm and 7 nm.

9. A method as claimed in any one of Claims 5 to 8, characterized in that the Ag layer on the surface of the Au nanorod is formed by mixing a first solution containing the Au nanorod with a second solution containing Ag, wherein the Au nanorod in the first solution is 100 ppm.

Ansprüche

1. Nanostruktur, dadurch gekennzeichnet, dass sie umfasst:

ein Au-Nanostäbchen;

eine Schale, die das Au-Nanostäbchen einkapselt und eine Au/Ag-Legierung ist; und

einen leeren Spalt, der eine Breite im Bereich von 1,0 nm bis 6,0 nm aufweist und der zwischen dem Au-Nanostäbchen und der Schale angeordnet ist,

wobei die Nanostruktur einen Nahe-Infrarotstrahl mit einer Wellenlänge von 1000 nm bis 1350 nm absorbiert.

2. Nanostruktur nach Anspruch 1, dadurch gekennzeichnet, dass die Nanostruktur zudem eine nichtlineare optische Eigenschaft zeigt und eine Zwei-Photonen-Fluoreszenz erzeugt.

3. Nanostruktur nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass die Nanostruktur eine kleinere Größe als 100 nm aufweist, und die Schale eine Dicke zwischen 2 nm und 7 nm aufweist.

4. Nanostruktur nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass die Nanostruktur zur Durchführung einer Bildanalyse und einer Medikamentenabgabe für ein Säugetier mit einem Photosensibilisator kombiniert wird.

5. Verfahren zur Herstellung einer Nanostruktur, dadurch gekennzeichnet, dass es folgende Schritte umfasst:

(a) Bereitstellen eines Au-Nanostäbchens mit einer Oberfläche;

(b) Bilden einer Ag-Schicht auf der Oberfläche des Au-Nanostäbchens; und

(c) Mischen des Au-Nanostäbchens und der Ag-Schicht mit einer 1 mM Au-Ionenlösung zur Bildung einer Kern-Schale-Struktur für die Nanostruktur, wobei das Volumen der Au-Ionen-Lösung 0,8- bis 2-mal so groß ist wie das des Au-Nanostäbchens,

und die Kern-Schale-Struktur einen Nahe-Infrarotstrahl mit einer Wellenlänge von 1000 nm bis 1350 nm absorbiert, und einen Kern, eine Schale und einen leeren Spalt umfasst, der zwischen dem Kern und der Schale ausgebildet ist, und eine Breite im Bereich von 1,0 nm bis 6,0 nm aufweist.

6. Verfahren nach Anspruch 5, dadurch gekennzeichnet, dass Schritt (c) zudem die Zugabe einer Ascorbinsäurelösung umfasst.

7. Verfahren nach Anspruch 5 oder 6, dadurch gekennzeichnet, dass die Au-Ionenlösung Chlorgoldsäure ist, deren Volumen 0,8- bis 1,5-mal so groß ist wie das des Au-Nanostäbchens.

8. Verfahren nach einem der Ansprüche 5 bis 7, dadurch gekennzeichnet, dass die Schale eine Dicke zwischen 2 nm und 7 nm aufweist.

9. Verfahren nach einem der Ansprüche 5 bis 8, dadurch gekennzeichnet, dass die Ag-Schicht auf der Oberfläche des Au-Nanostäbchens gebildet wird durch Mischen einer ersten Lösung, die das Au-Nanostäbchen enthält, mit einer zweiten Lösung, die Ag enthält, wobei das Au-Nanostäbchen in der ersten Lösung 100 ppm ausmacht.

Revendications

1. Nanostructure, caractérisé en ce qu'elle comprend :

une nanobaguette d'Au ;

une enveloppe encapsulant le nanobaguette d'Au et constituée d'un alliage d'Au/Ag ; et

un espace vide ayant une largeur de 1,0 nm à 6,0 nm, et situé entre la nanobaguette d'Au et l'enveloppe,

la nanostructure absorbant un rayonnement infrarouge proche de 1 000 nm à 1 350 nm de longueur d'onde.

2. Nanostructure selon la revendication 1, caractérisée en ce que la nanostructure présente en outre une propriété optique non linéaire et produit une fluorescence biphotonique.

3. Nanostructure selon la revendication 1 ou 2, caractérisée en ce que la nanostructure a une taille plus petite que 100 nm, et l'enveloppe a une épaisseur de 2 nm à 7 nm.

4. Nanostructure selon l'une quelconque des revendications 1 à 3, caractérisée en ce que la nanostructure est combinée avec un photosensibilisateur pour réaliser une analyse d'image et administrer un médicament à un mammifère.

5. Procédé de préparation d'une nanostructure, caractérisé en ce qu'il comprend les étapes qui consistent à :

(a) fournir une nanobaguette d'Au ayant une surface ;

(b) former une couche d'Ag sur la surface de la nanobaguette d'Au ; et

(c) mélanger la nanobaguette d'Au et la couche d'Ag avec une solution ionique d'Au de 1 mM pour former une structure noyau-enveloppe pour la nanostructure, la solution ionique d'Au ayant un volume de 0,8 à 2 fois celui de la nanobaguette d'Au et la structure noyau-enveloppe absorbant un rayonnement infrarouge proche de 1 000 nm à 1 350 nm de longueur d'onde, et comprenant un noyau, une enveloppe et un espace vide formé entre le noyau et l'enveloppe et ayant une largeur de 1,0 nm à 6,0 nm.

6. Procédé selon la revendication 5, caractérisé en ce que l'étape (c) comprend en outre une addition d'une solution d'acide ascorbique.

7. Procédé selon la revendication 5 ou 6, caractérisé en ce que la solution ionique d'Au est un acide chloraurique qui a un volume de 0,8 à 1,5 fois celui de la nanobaguette d'Au.

8. Procédé selon l'une quelconque des revendications 5 à 7, caractérisé en ce que l'enveloppe a une épaisseur de 2 nm à 7 nm.

9. Procédé selon l'une quelconque des revendications 5 à 8, caractérisé en ce que la couche d'Ag sur la surface de la nanobaguette d'Au est formée en mélangeant une première solution contenant la nanobaguette d'Au avec une deuxième solution contenant de l'Ag, la nanobaguette d'Au dans la première solution étant présente à un niveau de 100 ppm.

Drawing